4k2x

Publication Abstract from PubMed

Tetracyclines are a group of natural products sharing a linearly fused four-ring scaffold, which is essential for their broad-spectrum antibiotic activities. Formation of the key precursor anhydrotetracycline 3 during oxytetracycline 1 biosynthesis has been previously characterized. However, the enzymatic steps that transform 3 into 1, including the additional hydroxylation at C5 and the final C5a-C11a reduction, have remained elusive. Here we report two redox enzymes, OxyS and OxyR, are sufficient to convert 3 to 1. OxyS catalyzes two sequential hydroxylations at C6 and C5 positions of 3 with opposite stereochemistry, while OxyR catalyzes the C5a-C11a reduction using F420 as a cofactor to produce 1. The crystal structure of OxyS was obtained to provide insights into the tandem C6- and C5-hydroxylation steps. The substrate specificities of OxyS and OxyR were shown to influence the relative ratio of 1 and tetracycline 2.

Uncovering the Enzymes that Catalyze the Final Steps in Oxytetracycline Biosynthesis.,Wang P, Bashiri G, Gao X, Sawaya MR, Tang Y J Am Chem Soc. 2013 May 15;135(19):7138-7141. Epub 2013 May 1. PMID:23621493^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.